Diabetes mellitus is a metabolic disorder afflicting more than 29 million Americans. This disease manifests itself with abnormal blood glucose levels that lead to other significant health conditions including kidney failure, nerve damage, blindness, heart attack, and stroke. For more than 3 million diabetics using insulin to control hyperglycemia, frequent monitoring of blood glucose concentrations via finger prick testing is protocol for disease management. Intermittent sampling afforded by finger prick testing is inadequate due to the narrow glimpse of blood glucose concentrations provides. Much work, both academic and commercial, has focused on developing an implantable glucose biosensor that would allow for continuous blood glucose monitoring. However, even today's FDA-approved biosensors are prone to poor analytical performance and limited-use lifetimes due to the foreign body response. To remedy this, we are developing biosensors that slowly release low levels of nitric oxide (NO), a mediator of the foreign body response. In this Phase II SBIR Program, we will modify existing FDA-approved sensors with NO-release membranes, validate sensor performance in a diabetic pig model, subject our glucose sensor membranes to biocompatibility testing according to ISO-10993 standards; and, prepare for and file a request for designation (RFD) and a pre-submission with the U.S. Food and Drug Administration.